Rubin David T, Torres Joana, Regueiro Miguel, Reinisch Walter, Prideaux Lani, Kotze Paulo G, Tan Fiona H, Gardiner Sean, Mundayat Rajiv, Cadatal Mary Jane, Ng Siew C
Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal.
Crohns Colitis 360. 2024 Jan 20;6(1):otae004. doi: 10.1093/crocol/otae004. eCollection 2024 Jan.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program.
Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study.
This post hoc analysis included 1156 patients (ever smokers, = 416 [36.0%; current smokers, = 59 (5.1%); ex-smokers, = 357 (30.9%)]; never smokers, = 740 [64.0%]; median [range] treatment duration 654 [1-2712] and 615.5 [1-2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; infection, 12.0%; lower respiratory tract infection, 19.5%: corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers.
Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies.
NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.
托法替布是一种用于治疗溃疡性结肠炎（UC）的口服 Janus 激酶抑制剂。本分析评估了吸烟对 UC 临床研究中托法替布疗效和安全性的影响。
在 2 期诱导研究（仅基线人口统计学和安全性）、3 期研究（OCTAVE 诱导 1 和 2、OCTAVE 维持、OCTAVE 开放）以及 3/4b 期 RIVETING 研究中，根据吸烟状态（曾经吸烟者[当前吸烟者和既往吸烟者]和从不吸烟者）评估疗效终点和不良事件（AE）。
这项事后分析纳入了 1156 名患者（曾经吸烟者，n = 416 [36.0%]；当前吸烟者，n = 59 [5.1%]；既往吸烟者，n = 357 [30.9%]；从不吸烟者，n = 740 [64.0%]）；治疗持续时间中位数[范围]分别为 654 [1 - 2712]天和 615.5 [1 - 2850]天）。曾经吸烟者和从不吸烟者达到疗效终点的比例相似。88.7%的曾经吸烟者和 83.8%的从不吸烟者报告了不良事件。总体而言，60.6%的曾经吸烟者发生感染（严重感染，5.5%；带状疱疹[非严重和严重]，10.8%；感染，12.0%；下呼吸道感染，19.5%；从不吸烟者中的相应值分别为 53.1%、3.9%、6.8%、8.5%和 11.4%）。1.0%的曾经吸烟者和 0.7%的从不吸烟者报告了主要不良心血管事件，1.0%的曾经吸烟者和 0.9%的从不吸烟者报告了血栓栓塞事件（静脉和动脉）。曾经吸烟者（分别为 0.5%、2.5%和 3.7%）和从不吸烟者（分别为 0.1%、1.5%和 1.0%）中死亡、恶性肿瘤（不包括非黑色素瘤皮肤癌[NMSC]）和 NMSC 的发生频率较低。0.6%的从不吸烟者报告了结直肠癌；曾经吸烟者中未发生病例。
托法替布在曾经吸烟者和从不吸烟者中的疗效和安全性总体相似。总体而言，曾经吸烟者中严重不良事件以及如预期的感染比从不吸烟者更频繁。这可能为治疗选择和监测策略提供参考。
NCT00787202；NCT01465763；NCT01458951；NCT01458574；NCT01470612；NCT03281304。
